Expression of c-FLIP in Gastric Cancer and its Relation to Tumor Cell Proliferation and Apoptosis
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Abstract
Background : The expression of c-FLIP (cellular Fas-associated death domain-like interleukin-1 β-converting enzyme (FLICE)-inhibitory protein), which is a member of the family of inhibitors of apoptosis, has been associated with tumor development and progression. The aim of this study was to evaluate the expression of c-FLIP in gastric cancer and its correlation with tumor cell proliferation, apoptosis and the clinicopathologic features. Methods : Immunohistochemical staining with anti-c-FLIP antibody was performed in 98 tissue samples obtained from gastric cancer patients who underwent surgical treatment. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), and the proliferative cells were visualized by staining with Ki-67 antibody. Results : The positive expression of c-FLIP in the gastric cancer tissues was demonstrated in 57.1% of the cases. The expression of c-FLIP was increased in the gastric cancer tissues compared with the matched normal gastric mucosa. The expression of c-FLIP was significantly associated with histologic differentiation (p=0.038). However, there was no association between the c-FLIP expression and the other clinicopathological parameters, including patient survival. The Ki-67 labeling index (KI) for the 98 tumors ranged from 7.6 to 85.0 with a mean KI of 50.4±15.7. The mean KI value of the c-FLIP positive tumors was 54.1±15.3 and this was significantly higher than that of the c-FLIP negative tumors (p=0.005). The apoptotic index (AI) for the 98 tumors ranged from 0.0 to 10.0 with a mean AI of 7.4±2.3. There was no significant difference between the c-FLIP expression and the AI (p=0.347). Conclusions : These results suggest that the c-FLIP expression may be associated with tumor cell proliferation of gastric cancer.
참고문헌 (25)
- "Apoptosis in the pathogenesis and treatment of disease", 267, pp.1456~1462 (1995)
- "Death by dozens of cuts", 280, pp.32~34 (1998)
- "Apoptosis: biochemical aspects and clinical implications", 326, pp.27~45 (2002)
- "Caspase activation: the induced-proximity model", 96, pp.10964~10967 (1999)
- "Inhibition of fas death signals by FLIPs", 10, pp.552~558 (1998)
- "Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development", 12, pp.633~642 (2000)
- "The flip side of FLIP", 382, pp.e1~e3 (2004)
- "Targeting the FLICE inhibitory protein (FLIP) in cancer therapy", 3, pp.124~127 (2003)
- "Expression of cellular FLICE", caspase-8 inhibitory protein is associated with malignant potential in endometrial carcinoma, 2005, pp.15, 663~670
- "Expression of cellular FLICE-inhibitory protein and its association with p53 mutation in colon cancer", 11, pp.2482~2485 (2005)
- "c-FLIP expression in bladder urothelial carcinomas: its role in resistance to Fas-mediated apoptosis and clinicopathologic correlations", 63, pp.1198~1204 (2004)
- "Increased expression of FLIP, an inhibitor of Fas-mediated apoptosis, in stomach cancer", 111, pp.309~314 (2003)
- "Overexpression of cellular FLICE-inhibitory protein (FLIP) in gastric adenocarcinoma", 106, pp.397~405 (2004)
- "Hall PA. Detection of the Ki-67 antigen in fixed and wax-embedded sections with the monoclonal antibody MIB1. Histopathology 22", pp.355~360 (1993)
- "Vartanian R. Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel", pp.337~342 (1994)
- "Molecular biology of gastric carcinoma: from laboratory to bedside", 14, pp.1150~1160 (1999)
- "Lauren P. The two histologic main types of gastric carcinoma. Acta Pathol Microbiol Scand 64", pp.31~49 (1965)
- "Sobin LH. Histologic typing of oesophageal and gastric Tumors. In WHO International Histologic Classification of Tumors. Berlin" (1990), Springer-Verlag
- "Manual for staging cancer. In: Stomach cancer", pp.71~76 (1997), Philadelphia, Lippincott-Raven
- "Brigati DJ. Complete one-hour immunohistochemistry based on capillary action. Biotechniques 13", pp.434~443 (1992)
- "Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119", pp.493~501 (1992)
- "Dunlop D. Chromatin cleavage in apoptosis association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 142", pp.67~77 (1984)
- "c-FLIPL is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis", 21, pp.3704~3714 (2002)
- "The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex", 277, pp.45162~45171 (2002)
- "Activation of caspases-8 and -10 by c-FLIPL", 382, pp.651~657 (2004)